Remission In Rheumatoid Arthritis Research Articles

“It means almost forgetting that you've got a disease”: An OMERACT study to define independence in the context of rheumatoid arthritis remission from the patient perspective

AimsOur previous work identified pain, fatigue, and independence as missing from the ACR/EULAR rheumatoid arthritis (RA) remission criteria from the patient perspective. Validated measures exist for pain and fatigue, but not for independence. As a first step towards developing such a measure, this study aimed to understand ‘Independence’ in the context of RA remission from the patient perspective. MethodsInternational qualitative research study comprising five focus groups of 19 participants with RA. Data were analysed using reflexive thematic analysis. ResultsFive overarching themes were identified, underpinned by a construct of “stages of independence”. Independence means at least being ‘physically and functionally able’ but may go beyond this and enable ‘participation beyond function’, ‘cognitive independence’, and ‘having or taking control’. There was no agreement on whether assistance is an aid to independence or undermines ability to achieve independence (‘assistance is complicated’). The construct “Stages of independence” acknowledges that Independence may mean different things to different patients and there may be other factors beyond disease activity that hold patients in each of these stages. ConclusionThese novel data suggest a desirable definition of independence includes full active participation without the need to consider or work around disease activity, and cognitive independence from thoughts of RA. Independence in RA remission is a complex concept and next steps will be to seek patient and professional agreement on the most important issues raised in these focus groups to take forward to developing a measure for independence in the context of RA remission from the patient perspective.

Non-disability is reachable with advocating clinical deep remission in rheumatoid arthritis

Non-disability is reachable with advocating clinical deep remission in rheumatoid arthritis

Syndecan-1 Levels in Females with Active Rheumatoid Arthritis.

Background: The relationship between serum glycoprotein syndecan-1 and disease activity in rheumatoid arthritis (RA) is still unknown. This study aimed to evaluate whether serum syndecan-1 concentrations are associated with moderate/severe disease activity. Methods: Study Design: This was a cross-sectional study. Seventy-five adult women with RA were classified into (a) moderate/severe RA based on the disease activity score, using the erythrocyte sedimentation rate (DAS28-ESR ≥ 3.2, n = 50), and (b) RA in remission (DAS28-ESR < 2.6, n = 25). Twenty-five healthy women were taken as the reference group. Syndecan-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). High values of serum syndecan-1 levels (≥24 ng/mL) were used to identify the utility values of this biomarker. Results: The patients with RA had higher levels of syndecan-1 than the controls (p < 0.001). RA patients with active disease had higher syndecan-1 levels than RA patients in remission (57.6 vs. 23.5 ng/mL, respectively; p = 0.002). High syndecan-1 concentrations demonstrated the following utility values for identifying disease activity: sensitivity, 84% (95%CI: 71-93); specificity, 52% (95%CI: 31-72); positive predictive value, 78% (95%CI: 70-84); and negative predictive value, 62% (95%CI: 44-77). Conclusions: High syndecan-1 levels have good sensitivity and positive predictive value for identifying disease activity; however, their specificity is limited. Future prospective studies are needed to assess whether syndecan-1 levels can predict treatment failure in RA.

A COMPARISON BETWEEN ENTERAL AND PARENTERAL METHOTREXATE INTAKE IN IRAQI PATIENTS WITH RHEUMATOID ARTHRITIS REGARDING EFFICACY AND LIVER FUNCTION IMPAIRMENT

Objectives: Methotrexate (MTX) is a disease-modifying ant-rheumatic drug that has been used commonly in patients with rheumatoid arthritis (RA) with a goal of reducing RA activity or RA remission. Response to MTX varied among patients and side effects including liver impairment are not uncommon. The study aimed to compare oral and parenteral MTX intake regarding the efficacy and risk of liver impairment in patients with RA. Subject: Thirty patients who were newly diagnosed with RA according to EULAR/ASAR were included in the study. MTX was given for them for 6 months in a dose ranging between 2 and 25 mg either orally or parenterally intramuscular and subcutaneously once weekly. Patients were assessed depending on clinical disease activity index (CDAI) score and liver enzymes were measured before and after the start of the treatment. Results: The study showed that parenteral MTX intake significantly improves the CDAI score more than oral intake, CDAI reduced from 13.15±3.25 to 5.57±2.34 following 6 months of treatment in comparison to its’ insignificant reduction from 12.72±3.13 to 8.90±3.08 following oral treatment. Regarding liver enzymes, the impairment in alanine aminotransferase and aspartate aminotransferase is significantly less than that with oral ones with the same effect on alkaline phosphatase. Conclusion: Parenteral MTX intake tends to be more efficacious in attaining low disease activity than oral intake with a lower rate of impaired liver function.

Differences and Similarities in the Feet of Metatarsalgia Patients with and without Rheumatoid Arthritis in Remission.

Objectives: Metatarsalgia continues to be a problem in patients with rheumatoid arthritis (RA) in remission (remRA), as well as in the non-rheumatic population, with a mechanical origin. Identify and compare clinical, morphological, disability, synovitis (ultrasound), and radiological osteoarticular damage characteristics in two groups of patients with lesser-ray metar-tarsalgia, with remRA, and without RA. Methods: Cross-sectional study with 84 patients with remRA (mRA) and 60 patients without RA (nmRA). The study evaluated five clinical variables (pain, Foot Function Index (FFI), joint mobility, digital deformities, and foot type), a radiological variable (osteoarticular damage), and an ultrasound variable (metatarsal synovitis). The data were analysed using descriptive and correlational techniques. Results: There were no significant differences in sex, age, body mass index (BMI), or degree of pain. Both groups showed a high prevalence of limited joint mobility for the ankle and first metatarsal phalanx (DF1st MTPJ) and digital deformities, with no statistically significant differences. Similarly, there were no differences in lesser-ray synovitis. On the other hand, there were differences in mRA with greater disability and activity limitation (FFI), LDD (lesser-ray digital deformities) stiffness, first-ray deformities, radiological damage, synovitis in 1st MTPJ, and positive Doppler (five patients). Conclusions: Metatarsalgia presents similarities in both populations. Biomechanical factors may influence the symptoms and presence of synovitis in patients with RA in remission. Other characteristics are more frequent in mRA, which could be related to the disease; thus, future research should include both biomechanical and ultrasound exploration of the foot in the valuation of patients in remission.

Optical imaging (HandScan) can identify ultrasound remission in rheumatoid arthritis

BackgroundIdentifying remission is of high importance in rheumatoid arthritis (RA) because remission is associated with less structural progression. We investigated the efficacy of a new optical imaging device, HandScan, to identify RA remission, as defined by ultrasound (US).Methods61 RA patients were included. Disease activity was evaluated by clinical assessment and US, using gray-scale (GS) and Power Doppler (PD). HandScan determined unitary optical spectral transmission (OST) values for wrists, metacarpophalangeal and proximal interphalangeal joints. At the patient level, three composite HandScan (HS) scores were calculated: total HS score; disease activity score OST (DAS-OST) and DAS-OST without patient global assessment (PtGA). Using ROC curves, we determined HS cut-offs to identify US-defined remission.ResultsAt the joint level, unitary OST values significantly correlated with GS synovitis [odds ratio (OR) 2.43, p < 0.0001] and PD positivity (OR 3.72, p = 0.0002 ). At the patient level, total HS score and DAS-OST were significantly associated with all gray-scale US (GSUS) and power doppler US (PDUS) parameters evaluated (synovitis number and grade, synovial thickness, PD grade) (p < 0.05). The cut-off to identify US-defined remission at the joint level was of 0.92, giving an 81% sensitivity and a 96% positive predictive value (PPV). At the patient level, ROC-curves failed to identify a robust cut-off for the total HS score, but did identify a cut-off (3.68) for DAS-OST to identify US-defined remission, but with lower sensitivity (75%), specificity (56%) and PPV (67%).ConclusionsHandScan is a non-invasive optical imaging technique providing OST values that correlate with GSUS and PDUS parameters. In addition, HandScan is able to reliably identify US-defined remission in RA at the joint level, with a good sensitivity and high PPV. At the patient level, HandScan DAS-OST can also determine US remission (while total HS score failed to do so), but with lower performance.

Plasma mtDNA as a possible contributor to and biomarker of inflammation in rheumatoid arthritis

ObjectivesNeutrophil extracellular trap formation and cell-free DNA (cfDNA) contribute to the inflammation in rheumatoid arthritis (RA), but it is unknown if mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) is more abundant in the circulation. It is unclear if DNA concentration measurements may assist in clinical decision-making.MethodsThis single-center prospective observational study collected plasma from consecutive RA patients and healthy blood donors. Platelets were removed, and mtDNA and nDNA copy numbers were quantified by polymerase chain reaction (PCR).ResultsOne hundred six RA patients and 85 healthy controls (HC) were recruited. Circulating median mtDNA copy numbers were increased 19.4-fold in the plasma of patients with RA (median 1.1 x108 copies/mL) compared to HC (median 5.4 x106 copies/mL, p<0.0001). Receiver operating characteristics (ROC) curve analysis of mtDNA copy numbers identified RA patients with high sensitivity (92.5%) and specificity (89.4%) with an area under the curve (AUC) of 0.97, p <0.0001 and a positive likelihood ratio of 8.7.Demographic, serological (rheumatoid factor (RF) positivity, anti-citrullinated protein antibodies (ACPA) positivity) and treatment factors were not associated with DNA concentrations. mtDNA plasma concentrations, however, correlated significantly with disease activity score-28- erythrocyte sedimentation rate (DAS28-ESR) and increased numerically with increasing DAS28-ESR and clinical disease activity index (CDAI) activity. MtDNA copy numbers also discriminated RA in remission (DAS28 <2.6) from HC (p<0.0001). Also, a correlation was observed between mtDNA and the ESR (p = 0.006, R= 0.29). Similar analyses showed no significance for nDNA.ConclusionIn contrast to nDNA, mtDNA is significantly elevated in the plasma of RA patients compared with HC. Regardless of RA activity, the abundance of circulating mtDNA is a sensitive discriminator between RA patients and HC. Further validation of the diagnostic value of mtDNA testing is required.

Tofacitinib as a means of optimizing the treatment of rheumatoid arthritis at the outpatient stage (clinical cases)

Two clinical cases of tofacitinib use in the management of rheumatoid arthritis (RA) patients by a rheumatologist at the outpatient stage within the framework of the “Treatment to Target” strategy are presented. The first clinical case describes the case history of a female patient (age 48 years, RA duration 20 years), which demonstrates the difficulties in selecting pathogenetic therapy for late-stage RA. Consecutively prescribed four synthetic baseline anti-inflammatory drugs (methotrexate, sulfasalazine, cyclophosphamide, leflunomide) and two genetically engineered biological drugs (infliximab, rituximab) failed to achieve remission of the disease in the patient. Decrease in disease activity was noted after connection of the third biological drug – etanercept, treatment with which had to be interrupted due to pregnancy planning. The return to the combined treatment after childbirth did not lead to repeated “success”. A positive result was achieved 12 weeks after tofacitinib at a dose of 10 mg/day, which provided a decrease in RA activity to moderate and complete withdrawal of glucocorticoids. Given the incomplete clinical effect, tofacitinib dose was increased to 20 mg/day by the outpatient rheumatologist, which resulted in achieving low RA activity persisting for 5 years. The second case demonstrates the effectiveness of tofacitinib inclusion in the RA treatment regimen as a “second-line” drug. A patient (age 46 years, RA duration 10 years) with long-term drug (methotrexate 25 mg/week) clinical and laboratory remission of RA after an upper respiratory tract infection developed an exacerbation of the disease. Despite three-component therapy with baseline anti-inflammatory drugs, the patient had persistence of high RA activity, which led to the revision of pathogenetic therapy – tofacitinib at a dose of 10 mg/day with clinical effect of the drug after 4 weeks. The achieved clinical and laboratory remission of the disease has been maintained for two years. In outpatient practice tofacitinib can be an effective tool for optimizing RA treatment.

Clinical disease activity index versus disease activity score (28 joints) for assessment of disease activity in obese patients of rheumatoid arthritis

Background: Measurement of disease activity by Disease Activity Score 28 joints -Erythrocyte Sedimentation Rate (DAS28-ESR), Disease Activity Score (28 joints)-C-Reactive Protein (DAS28-CRP), and Clinical Disease Activity Index (CDAI) has become an integral part of management of Rheumatoid Arthritis (RA), by ‘Treatment to Target’ approach. With the exception of CDAI, the other two use inflammatory markers ESR and CRP to measure disease activity. Obesity is also known to increase inflammatory markers like CRP. We undertake this study to examine if obesity confounds the disease activity measurement in RA leading to overestimation of disease activity. Methods: A cross-sectional observation study was conducted on one hundred patients of RA (40 obese and 60 non obese) in remission or low disease activity as defined by CDAI. They were divided into obese and non-obese groups based on Indian standards (BMI&gt;25kg/m2). ESR and CRP were measured in both the groups. DAS28-ESR and DAS28-CRP were calculated and compared using relevant statistical tests. Results: DAS28-ESR and DAS-28-CRP scores were significantly higher in the obese subjects, despite both groups having comparable CDAI scores. Similar findings were also observed with inflammatory markers ESR and CRP, both being higher in obese patients. Conclusions: We conclude that indices incorporating inflammatory markers, like DAS28 overestimate disease activity in obese RA patients. Treatment decisions regarding escalation or addition of DMARDs should be taken after considering the same. CDAI appears to be better suited for disease activity measurements in obese RA patients as compared to DAS 28.

Effects of tapering conventional synthetic disease-modifying antirheumatic drugs to drug-free remission versus stable treatment in rheumatoid arthritis (ARCTIC REWIND): 3-year results from an open-label, randomised controlled, non-inferiority trial

Tapering of disease-modifying antirheumatic drugs (DMARDs) to drug-free remission is an attractive treatment goal for patients with rheumatoid arthritis, although long-term effects of tapering and withdrawal remain unclear. We compared 3-year risks of flare between three conventional synthetic DMARD treatment strategies in patients with rheumatoid arthritis in sustained remission. In this open-label, randomised controlled, non-inferiority trial, we enrolled patients aged 18-80 years with rheumatoid arthritis who had been in sustained remission for at least 1 year on stable conventional synthetic DMARD therapy. Patients from ten hospitals in Norway were randomly assigned (2:1:1) with centre stratification to receive stable conventional synthetic DMARDs, half-dose conventional synthetic DMARDs, or half-dose conventional synthetic DMARDs for 1 year followed by withdrawal of all conventional synthetic DMARDs. The primary endpoint of this part of the study was disease flare over 3 years, analysed as flare-free survival and risk difference in the per-protocol population with a non-inferiority margin of 20%. This trial is registered with ClinicalTrials.gov (NCT01881308) and is completed. Between June 17, 2013, and June 18, 2018, 160 patients were enrolled and randomly assigned to receive stable-dose conventional synthetic DMARDs (n=80), half-dose conventional synthetic DMARDs (n=42), or half-dose conventional synthetic DMARDs tapering to withdrawal (n=38). Four patients did not receive the intervention and 156 patients received the allocated treatment strategy. One patient was excluded due to major protocol violation and 155 patients were included in the per-protocol analysis. 104 (67%) of 156 patients were women and 52 (33%) were men. 139 patients completed 3-years follow-up without major protocol violation; 68 (87%) of 78 patients in the stable-dose group, 36 (88%) of 41 patients in the half-dose group and 35 (95%) of 37 patients in the half-dose tapering to withdrawal group. During the 3-year study period, 80% (95% CI 69-88%) were flare-free in the stable-dose group, compared with 57% (41-71%) in the half-dose group and 38% (22-53%) in the half-dose tapering to withdrawal group. Compared with stable-dose conventional synthetic DMARDs, the risk difference of flare was 23% (95% CI 6-41%, p=0·010) in the half-dose group and 40% (22-58%, p<0·0001) in the half-dose tapering to withdrawal group, non-inferiority was therefore not shown. Adverse events were reported in 65 (83%) of 78 patients in the stable-dose group, 36 (90%) of 40 patients in the half-dose group, and 36 (97%) of 37 patients in the half-dose tapering to withdrawal group. One death occurred in the stable-dose conventional synthetic DMARD group (sudden death considered unlikely related to the study medication). Two conventional synthetic DMARD tapering strategies were associated with significantly lower rates of flare-free survival compared with stable conventional synthetic DMARD treatment, and the data do not support non-inferiority. However, drug-free remission was achiveable for a significant subgroup of patients. This trial provides information on risk and benefits of different treatment strategies important for shared decision making. Research Council of Norway and South-Eastern Norway Regional Health Authority.

Deconvolution of synovial myeloid cell subsets across pathotypes and role of COL3A1+ macrophages in rheumatoid arthritis remission.

Monocyte/macrophage (Mo/Mp) is a critical cell population involved in immune modulation of rheumatoid synovitis (RA) across different pathotypes. This study aims to investigate the contribution of Mo/Mp clusters to RA activity, and the biological function of particular subtypes in RA remission. We integrated single-cell RNA sequencing datasets from 4 published and 1 in-house studies using Liger selected by comparison. We estimated the abundance of Mo/Mp subtypes in bulk RNA-seq data from the 81 patients of the Pathobiology of Early Arthritis Cohort (PEAC) using deconvolution analysis. Correlations between Mo/Mp subtypes and RA clinical metrics were assessed. A particular cell type was identified using multicolor immunofluorescence and flow cytometry in vivo and successfully induced from a cell line in vitro. Potential immune modulation function of it was performed using immunohistochemical staining, adhesion assay, and RT-qPCR. We identified 8 Mo/Mp clusters. As a particular subtype among them, COL3A1+ Mp (CD68+, COL3A1+, ACTA2-) enriched in myeloid pathotype and negatively correlated with RA severity metrics in all pathotypes. Flow cytometry and multicolor immunofluorescence evidenced the enrichment and M2-like phenotype of COL3A1+ Mp in the myeloid pathotype. Further assays suggested that COL3A1+ Mp potentially attenuates RA severity via expressing anti-inflammatory cytokines, enhancing Mp adhesion, and forming a physical barrier at the synovial lining. This study reported unexplored associations between different pathologies and myeloid cell subtypes. We also identified a fibroblast-and-M2-like cluster named COL3A1+ Mp, which potentially contributes to synovial immune homeostasis. Targeting the development of COL3A1+ Mp may hold promise for inducing RA remission.

Biomarker combination predicting imminent relapse after discontinuation of biological drugs in patients with rheumatoid arthritis in remission.

Compared to conventional disease-modifying antirheumatic drugs (DMARDs), biological DMARDs demonstrate superior efficacy but come with higher costs and increased infection risks. The ability to stop and resume biological DMARD treatment while maintaining remission would significantly alleviate these barriers and anxieties. The objective of this study was to identify biomarkers that can predict an imminent relapse, hopefully enabling the timely resumption of biological DMARDs before relapse occurs. Forty patients with rheumatoid arthritis who had been in remission for more than 12 months were included in the study. The patients discontinued their biological DMARD treatment and were monitored monthly for the next 24 months. Out of the 40 patients, 14 (35%) remained in remission at the end of the 24-month period, while 26 (65%) experienced relapses at different time points. Among the relapse cases, 13 patients experienced early relapse within 6 months, and another 13 patients had late relapse between 6 months and 24 months. Seventy-three cytokines in the sera collected longitudinally from the 13 patients with late relapse were measured by multiplex immunoassay. Using cytokines at two time points, immediately after withdrawal and just before relapse, volcano plot and area under the receiver operating characteristic curves (AUC) were drawn to select cytokines that distinguished imminent relapse. Univariate and multivariate logistic regression analyses were used for the imminent relapse prediction model. IL-6, IL-29, MMP-3, and thymic stromal lymphopoietin (TSLP) were selected as potential biomarkers for imminent relapse prediction. All four cytokines were upregulated at imminent relapse time point. Univariate and multivariate logistic regression showed that a combination model with IL-6, MMP-3, and TSLP yielded an AUC of 0.828 as top predictors of imminent relapse. This methodology allows for the prediction of imminent relapse while patients are in remission, potentially enabling the implementation of on- and off-treatments while maintaining remission. It also helps alleviate patient anxiety regarding the high cost and infection risks associated with biological DMARDs, which are the main obstacles to benefiting from their superb efficacy.

The relationship between disease activity with pan-immune-inflammatory value and systemic immune-inflammation index in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Immune system cells have an important role in RA. Our aim was to investigate the relationship between disease activity, systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) levels in RA patients. We planned to investigate whether these 2 measurements have an advantage over each other. About 67 patients diagnosed with RA and 49 healthy controls included in this study. RA was diagnosed based on 2010 ACR classification criteria. In this cross-sectional study, peripheral blood tests, C-reactive protein (CRP), hemogram, and erythrocyte sedimentation rate levels were noted after the physical examination of all participants. PIV was calculated with the formula: (neutrophil count × platelet count × monocyte count) / lymphocyte count. SII was calculated as follows: (neutrophil count × monocytes count) / lymphocyte count. The disease activity score 28 (DAS28) were noted in patients with RA. CRP values of active RA group were significantly higher than remission RA and control groups (P < .001), control and remission RA groups were similar (P = .86). PIV and SII are significantly higher in active RA than remission RA and control (P < .001, P < .001) higher in remission RA than control (P < .001, P < .001). Receiver operating characteristic curve analysis in predicting remission compared to the control group, CRP was not significant, PIV and SII was significant and PIV has higher sensitivity and sensitivity, a PIV value of > 217.31 have sensitivity 75.0% and specificity 85.7%. CRP, PIV, and SII are statistically significant in predicting active RA compared to the remission RA and control group. Our findings show that PIV, and SII are easy, inexpensive and reliable markers predicting remission in RA patients. CRP was not significant compared to remission RA and control group, PIV and SII was significant and PIV has higher sensitivity and specificity than SII in the remission group in RA. Patients with high disease activity, PIV, SII, and CRP levels were effective in showing disease activity compared to RA remission group and healthy controls.

Dynamics of modified cardiovascular risk factors in patients with rheumatoid arthritis on the background of 5-year therapy with an interleukin 6 receptor inhibitor

The effect of an inhibitor of interleukin (IL) 6 receptors on the state of the cardiovascular system in patients with rheumatoid arthritis (RA) remains poorly understood, especially with its long-term use.The aim – to study the effect of therapy with the IL-6 receptor inhibitor tocilizumab (TCZ) on the dynamics of modifiable risk factors (RF), total cardiovascular risk (CVR), structural changes in the carotid arteries (CA) and the incidence of cardiovascular complications (CVC) in patients with rheumatoid arthritis during the 260-week follow-up period.Material and methods. The study included 37 patients with active RA (32 women and 5 men) with ineffectiveness and/or intolerance to disease modifying anti-rheumatic drugs (DMARDs); median age was 56 [48; 68] years, disease duration was 92 [49; 158] months; DAS28 (Disease Activity Score 28) – 6.2 [5.5; 6.7] points; all patients were seropositive for rheumatoid factor (RF), 86% – for antibodies to cyclic citrullinated peptide (ACCP). Patients received TCZ therapy 8 mg/kg intravenously every 4 weeks; after 192 [176; 210] weeks, 60% of patients switched to subcutaneous administration of the drug at a dose of 162 mg once a week. In 51% of patients with RA, TCZ monotherapy was performed, in 49% – combination therapy of TCZ with DMARDs. Statins were received by 17 (46%) patients, including 7 patients before and 10 after inclusion in the study. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE scale, atherosclerotic vascular lesions were assessed by the detection of atherosclerotic plaques (ASP) of CA. The observation period was 260.4 [251.5; 283.4] weeks.Results. After 260 weeks of TCZ therapy, RA remission was observed in 32 (86%) patients, low activity – in 5 (14%) patients. During the observation period, the frequency of modified RF and the total CVR did not change significantly, an increase in body mass index (BMI) by 11% was recorded, the number of patients with hypercholesterolemia and a reduced level of HDL cholesterol (C) decreased. In patients without statin therapy, there were no significant changes in the blood lipid spectrum. In the group of patients receiving statins, there was an increase in HDL-C by 43%, a decrease in cholesterol levels by 15%, atherogenic index (AI) by 56% (p&lt;0.01 in all cases) and associations between the dynamics of ∆cholesterol and ∆CRP (r=0.35; p=0.04), ∆LDL-C and ∆CRP (r=0.41; p=0.03). Significant structural changes in CA in RA patients by the end of 260 weeks of TCZ therapy were not identified. Initially, intima-media thickness (IMT) CA positively moderately correlated with age (r=0.7; p&lt;0.01), BMI (r=0.37; p&lt;0.01), systolic blood pressure (SBP) (r=0.62; p&lt;0.01) and weakly with lipid spectrum parameters – cholesterol (r=0.29; p&lt;0.01), LDL-C (r=0.36; p&lt;0.01). No new associations of IMT CA by the end of the observation, as well as the relationship of the IMT CA value with the indicators of RA activity and the ongoing therapy, were identified. By the end of the study, the distribution of patients by mSCORE value and CVR level did not change significantly. The incidence of CVC was 0,54 per 100 patient-years over a 260-week period of TCZ use. Conclusion. Against the background of long-term TCZ therapy in RA patients, there was no increase in CVR and significant structural changes in CA. It is necessary to dynamically monitor the blood lipid profile and CVR in RA patients receiving TCZ therapy. Statin therapy can successfully control dyslipidemia in RA patients who receive long-term TCZ.

ALOX5 drives the pyroptosis of CD4+ T cells and tissue inflammation in rheumatoid arthritis.

Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4+ T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A4 (LTA4), were increased in CD4+ T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4+ T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4+ T cells enhanced the production of the LTA4 derivative LTB4, which stimulated Ca2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.

Prevention of Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Persistent Low-grade In-flammation May be an Impediment Needing Attention

Objective: To determine the status of ‘residual inflammatory risk’ (RIR) and ‘residual cholesterol risk’ (RCR) in patients with Rheumatoid Arthritis (RA) in remission with the aim of estimating their atheroscle-rotic cardiovascular disease (ASCVD) risk. Methods: The study included patients with RA in remission during their last two clinic visits on treatment with disease- mod-ifying anti-rheumatic drugs (DMARDs). Using the QRISK-3 calculator, participants were stratified into four risk categories for ASCVD: ‘Very high’, ‘High’, ‘Moderate’, and ‘Low’. Patients were prescribed lipid-lowering drugs targeting low-density lipoprotein cholesterol (LDL-C) levels to &lt;50 mg/dl, &lt;70 mg/dl, &lt;100 mg/dl or &lt;130 mg/dl, respectively. Those with a history of ASCVD before or during the follow-up period was excluded from the study. Multimorbidity were also recorded in all the patients. Results: The study included 130 patients with RA in remission. The results showed that despite being in remission and taking treatment for lipid control, 81 (62%) and 91 (70%) patients still had ‘RIR’ and ‘RCR’, respectively. Hypertension, hypothyroidism, type-2 diabetes mellitus and obesity were the common multimorbidity. Conclusions: Persistent RIR in 62% of patients despite being in remission, could possibly be due to the current ‘liberal’ definition of RA permitting hs-CRP level up to &lt;10 mg/l, which is five-fold higher than the recommended &lt;2 mg/l for ASCVD prevention. Hence it may be necessary to revise the definition of ‘remission’ in RA factoring in the suggested lower level of hs-CRP. Additionally, rheumatologists might need to be more vigilant in lipid management with appropriate patient education regarding RCR.

Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission.

Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare - CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells - further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention.

Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis

ObjectivesLong-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify...

Characteristics and prevalence of clinical remission of rheumatoid arthritis in a nationwide study from Indonesia

AbstractAimTo investigate the clinical characteristics, DMARD treatment pattern, remission rate, and factors associated with disease remission of rheumatoid arthritis (RA) patients in Indonesia.MethodA multicenter survey was conducted in 2019–2020 involving 16 hospitals in Indonesia. Inclusion criteria were RA patients who fulfilled the 2010 ACR/EULAR classification criteria, were aged ≥18 years, and have been treated with 1 DMARD or more for at least 6 months, with exclusion criteria being the co‐existence of other autoimmune diseases or pain syndromes. Disease activities and remission rate were defined using DAS28‐ESR.ResultsA total of 870 patients were completed for analysis. Remission was achieved in 24.5% of patients, while low disease activity in 18.5%, moderate disease activity in 44.6%, and high disease activity in 12.4%. The distribution of conventional DMARDs from subjects was methotrexate 69.9%, leflunomide 15.9%, sulfasalazine 12.0%, chloroquine/hydroxychloroquine 8.9%, and cyclosporine 4.8%. Patients treated with biologic DMARDs were only 0.3%. The mean methotrexate dose was 11.2 ± 4.0 mg/week, and the mean methotrexate duration was 45.1 ± 36.6 months. The majority of patients received glucocorticoids (65.5%). 71.1% received DMARD monotherapy, while 28.9% had combined DMARDs. According to the multivariate analysis, delayed time to diagnosis and treatment (&gt;6 months), DMARD monotherapy, and glucocorticoid use were negatively associated with disease remission.ConclusionThe remission rate of Indonesian RA patients is 24.5%, and low disease activity is 18.5%. Methotrexate and leflunomide are the most frequent conventional DMARDs used. Delayed diagnosis, delayed treatment, and DMARD monotherapy contributed to the current low remission rate in Indonesia.

Intensive training programme for ultrasound-guided minimally invasive synovial tissue biopsy on knees and wrists in different phases of inflammation

ObjectivesTo develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality...